ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection |
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| Authors: | Raoel Maan Adriaan J. van der Meer Willem Pieter Brouwer Elisabeth P. C. Plompen Milan J. Sonneveld Robert Roomer Annemiek A. van der Eijk Zwier M. A. Groothuismink Bettina E. Hansen Bart J. Veldt Harry L. A. Janssen Andre Boonstra Robert J. de Knegt |
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| Affiliation: | 1 Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands, ; 2 Department of Viroscience, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands, ; 3 Toronto Centre for Liver Disease, Toronto Western & General Hospital, University Health Network, Toronto, Canada, ; National Taiwan University Hospital, TAIWAN, |
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| Abstract: | Background/ObjectiveGenetic polymorphisms in the inosine triphosphatase (ITPA) gene have been associated with the protection from early ribavirin(RBV)-induced hemolytic anemia among patients with chronic hepatitis C virus (HCV) infection. The aim of the present study was to investigate the association between the functional ITPA variants and hematological side effects during antiviral therapy with pegylated interferon (PegIFN) and RBV.ResultsIn total, 213 patients were included. The predicted ITPase activity was normal among 152 (71%) patients; 61 (29%) patients had ITPase deficiency. By multivariable linear regression, RBV dose in mg per kilogram (Beta 0.09, 95%CI 0.04–0.13, p<0.001) and normal ITPase activity (Beta 0.89, 95%CI 0.64–1.14, p<0.001) were associated with more Hb decline at week 4 of treatment. Patients with normal ITPase activity underwent more dose adjustments of RBV than patients with ITPase deficiency (19(13%) vs 1(2%),p = 0.014) and received erythropoietin more frequently (12 (8%) vs 0 (0%),p = 0.024).ConclusionGenetic variants in the ITPA gene protected against RBV treatment-induced anemia among Caucasian patients with chronic HCV infection. Patients with normal ITPase activity underwent more dose reductions of RBV and received erythropoietin more frequently. |
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